Methods

Study selection and assessment: Randomized controlled trials (RCTs) in any language that evaluated fenoldopam in critically
ill patients (surgical or intensive care unit [ICU]). Studies related to renal protection
in the setting of angiographic contrast media exposure were excluded. 16 RCTs (n = 1290) met the selection criteria. Fenoldopam dosages ranged from 0.025 to
0.1 µg/kg per minute; 1 trial used 0.3 µg/kg per minute. Control group treatment was
placebo (10 RCTs) or best available treatment (usually low-dose dopamine [5 RCTs])
or was not reported (1 RCT). Assessments of the quality of individual studies were
based on the Cochrane Handbook and included assessing risks for selection, performance,
attrition, and adjudication biases and allocation concealment.

Commentary

Augmenting renal blood flow is an attractive strategy for prevention and early treatment
of ARF in high-risk patients. Low-dose dopamine, which acts on several adrenergic
and dopaminergic receptors in a dose-dependent manner, has been extensively studied
for this purpose. Pooled data show that dopamine improves renal physiology, but these
effects are small and temporary and do not improve clinical outcomes (1). In contrast to dopamine, the newer agent, fenoldopam, vasodilates renal arterioles
by binding to DA-1 receptors more selectively.

The comprehensive systematic review by Landoni and colleagues evaluated fenoldopam
to prevent ARF in critically ill patients in the ICU and having surgery. Pooled analyses
suggested patient-important benefits (decreased renal replacement therapy and mortality)
and a clinically tolerable increased risk for hypotension. Although the authors included
RCTs in which the control group received active therapy, estimates of treatment effect
were similar when analyses were restricted to placebo-controlled RCTs. However, most
trials were small (only 5 enrolled > 100 patients), limiting the number
of outcome events, and most had low-to-moderate methodological quality. The estimates
of treatment effect may, therefore, be overly optimistic. Industry funding, another
potential source of bias, was not discussed. Furthermore, the review excluded contrast-induced
nephropathy, and a recent RCT of 315 patients showed that fenoldopam did not prevent
this complication in high-risk patients (2). Although physiologic arguments may support the efficacy of fenoldopam in ischemic
but not contrast-induced renal injury, this lack of consistency may simply reflect
methodological limitations of the RCTs included in the review.

Fenoldopam is a promising therapy for ARF. Given the limitations of current evidence,
we agree with the authors that a large multicentered RCT powered to detect improvements
in patient-important outcomes is justified and required.